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Abstract: Cancer is a significant public health problem worldwide. The global cancer burden is expected to be 28.4 million cases in 2040. With the advent of technology, there has been significant progress in cancer treatment over the past few decades. However, the struggle against cancer continues. Focusing on the current vaccines available for virally associated cancers, this article briefly talks about the development and mechanism of action of Hepatitis B vaccine and Human Papilloma Virus vaccine, and the potential vaccinology for other related cancers like head and neck cancer based on mRNA technology.
In the pursuit of discovering effective treatments against a significant cause of mortality worldwide, vigorous research has been performed relentlessly on Cancer Vaccines for about 40 years now (1). Cancer Vaccines are a part of contemporary immunotherapy, which, like essential vaccines, work on the principle of eliciting immunity to tumour antigens and keeping a memory to prevent neoplasia later.
According to 2020 statistics, cancer accounts for 10 million deaths worldwide, out of which human papillomavirus (HPV) and hepatitis are responsible for approximately 30% of cancer cases in low- and lower-middle-income countries (2). Cervical cancer, caused by human papillomavirus, is the second most common cancer in women worldwide and a leading cause of death by cancer, accounting for 74,000 deaths annually in India (3). HPV also causes vaginal, vulvar, anal, and oral cancers. Likewise, chronic hepatitis B and C is responsible for 80% of the second most common cause of cancer death globally, liver cancer (4).
Although the genetic mechanisms of oncogenesis by HPV are still not adequately elucidated, a few theories have been put forward. The high-risk HPV types, which primarily includes HPV 16, 18, 45, and 56, are known to potentially cause vital transformation in the host cell DNA by E6 and E7 viral proteins, which eliminate the tumour suppressors p53 and Rb, resulting in anti-apoptosis, genetic instability, and formation of tumour lesions (5). Hepatitis B virus is associated with hepatocellular carcinoma (HCC). Chronic HBV infection leads to deregulation of numerous signalling pathways of the cell cycle, and the presence of X protein (HBx) and HBV large and middle envelope proteins (LHBs & MHBs), accompanied by inflammation in the liver, play a crucial role in the development of HCC (6).
Talking about the vaccines, the HBV vaccine is the first cancer vaccine; however, no such vaccine is available for HCV yet (4). There are two types of vaccines available globally for HBV; plasma-derived and genetically engineered, commercially available under Heptavax-B and Recombivax HB. Fundamentally, both vaccines work on the notion of inducing the production of antibodies by presenting HBsAg surface antigen of HBV, offering protection against all genotypes of HBV, and there is almost no difference in their respective efficacies (7). Hepatitis B vaccines are also sold under other brand names like Enger ix B and Heplisav B.
Gardasil (2006) and Cervarix (2007) are the two vaccines effective against HPV, produced by recombinant DNA technology, which deploys strongly immunogenic virus-like particles (VLPs) made of HPV surface proteins, lacking the viral DNA (3, 8). Gardasil 9 (2014) and Cecolin (2020) are two neoteric HPV vaccines with a higher efficacy (9). The former could prevent 85–95% of HPV-related vulvar, vaginal, and anal cancers and 90% of genital warts and is licensed for the male population (9, 10).
The current trend shows a dramatic increase in HPV-driven cancers like Head and Neck cancer (HNC) or Oropharyngeal cancer. Prophylactic vaccines already available for HPV are under clinical trials for HPV- positive HNC. However, these vaccines are not theoretically effective for HPV- negative HNC, which is usually a consequence of excessive alcohol, smoking, and tobacco consumption or having a genetic background (11).
Lately, as the global pandemic has directed the spotlight on messenger RNA, the concept of mRNA cancer vaccines, similar to pre-existing DNA or peptide vaccines, has caught attention. mRNA technology is pertinent for cancer vaccinology as it fulfils the perquisites, speedy design, and rapid manufacturing. For HNC so far, personalized mRNA vaccines are being produced for patients based on the specific molecular features of their tumours, distinguished by collecting their tissue samples. In a recent clinical trial testing on patients with advanced HNC, groundbreaking results have been observed. For example, 20% of the patients had all signs of their tumours disappear following the treatment, and the other 50% showed shrinkage in their tumours (12). Even though a minimal number of patients were taken into account for the trial, researchers are cautiously optimistic about the potential of mRNA vaccines to prevent neoplasia associated with viruses, to the least.
Cancers of the Urinary Bladder, Prostate gland, Colon-Rectum, and Skin are a few other examples of cancers on which extensive research is under progress to develop prophylactic or therapeutic vaccines (13). Throughout this endeavour of uncovering modern therapeutics for battling cancer, scientists have come across innumerable hurdles, including advanced asymptomatic metastatic tumours and the formerly suppressed immune system of the majority of patients. Nevertheless, such remarkable advances in cancer immunology have highlighted that cancer vaccinology could be a promising way of treating many prevailing tumours. Still, at the same time, it needs to be worked upon relentlessly.
References
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Hepatitis B Foundation: History of Hepatitis B Vaccine. (2022). Retrieved 19 February 2022, from https://www.hepb.org/prevention-and-diagnosis/vaccination/history-of-hepatitis-b-vaccine/
Tulay, P., & Serakinci, N. (2016). The role of human papillomaviruses in cancer progression. Journal Of Cancer Metastasis And Treatment, 2(6), 201. DOI: 10.20517/2394-4722.2015.67
Torresi, J., Tran, B., Christiansen, D., Earnest-Silveira, L., Schwab, R., & Vincan, E. (2019). HBV-related hepatocarcinogenesis: the role of signaling pathways and innovative ex vivo research models. BMC Cancer, 19(1). DOI: 10.1186/s12885-019-5916-6
(2022). Retrieved 20 February 2022, from https://apps.who.int/iris/bitstream/handle/10665/205655/B3368.pdf?sequence=1
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Markowitz, L., & Schiller, J. (2021). Human Papillomavirus Vaccines. The Journal Of Infectious Diseases, 224(Supplement_4), S367-S378. DOI: 10.1093/indices/jiaa621
9-Valent human papillomavirus vaccine: a review of the clinical development program. (2022). Expert Review Of Vaccines. Retrieved from https://www.tandfonline.com/doi/full/10.1080/14760584.2017.1383158?scroll=top&needAccess=true
Wang, C., Dickie, J., Sutavani, R., Pointer, C., Thomas, G., & Savelyeva, N. (2018). Targeting Head and Neck Cancer by Vaccination. Frontiers In Immunology, 9. doi: 10.3389/fimmu.2018.00830
How mRNA Vaccines Might Help Treat Cancer. (2022). Retrieved 20 February 2022, from https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer
What is Cancer Vaccines?. (2013). Retrieved 20 February 2022, from https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/what-are-cancer-vaccines
About the Author
Author: Jayanti Chhillar
Bio: Jayanti Chhillar is a final year student, studying B.Sc. (H) Biological Sciences at Sri Venkateswara College, University of Delhi. As a curious kid, she always found intricate cellular and molecular mechanisms and their biochemical pathways fascinating, following which, she aims to pursue higher studies in the field of Molecular Biology and Cancer Therapeutics. Stem cells and Induced Pluripotent Cells is another promising domain of research that she finds extremely captivating and innovative. Inquisitive about, intracellular signalling and functioning, she wants to explore ways by which they can be manipulated for clinical purposes, and consequently develop better medications and contemporary treatments for Cancer.
She loves to interact with like-minded people, understand their perspectives and discuss and learn more about science in general, which is primarily why she’s eagerly looking forward to joining the TSV team.
Editor: Aarushi Chitkara
Illustrator: Himanshi Yadav
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